title: Pyrrolo[3,4-h]quinolinones a new class of photochemotherapeutic agents.
abstract: Pyrrolo[3,4-h]quinolin-2-ones were synthesized as nitrogen isosters of the angular furocoumarin angelicin, with the aim of obtaining new photochemotherapeutic agents with increased antiproliferative activity and lower undesired toxic effects. A versatile synthetic pathway was approached to allow the isolation of derivatives of the new ring system with a good substitution pattern on the pyrrole moiety. Photobiological screenings of the new compounds revealed a potent phototoxic effect and a great UVA dose dependence, reaching IC(50) values at submicromolar level. The induced cellular photocytotoxicity was related to apoptosis with the involvement of mitochondria and lysosomes, alteration of cell cycle profile and membrane lipid peroxidation.
authors.affiliation: Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari, Sezione di Chimica Farmaceutica e Biologica, Università degli Studi di Palermo, Via Archirafi 32, Palermo 90123, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Barraja
authors.forename: Patrizia
authors.initials: P
authors.lastname: Diana
authors.forename: Alessandra
authors.initials: A
authors.lastname: Montalbano
authors.forename: Anna
authors.initials: A
authors.lastname: Carbone
authors.forename: Giampietro
authors.initials: G
authors.lastname: Viola
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.forename: Alessia
authors.initials: A
authors.lastname: Salvador
authors.forename: Daniela
authors.initials: D
authors.lastname: Vedaldi
authors.forename: Francesco
authors.initials: F
authors.lastname: Dall'Acqua
authors.forename: Girolamo
authors.initials: G
authors.lastname: Cirrincione
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry / Q000187:drug effects / Q000528:radiation effects; D005470:Fluorometry; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D015227:Lipid Peroxidation; D010718:Phosphatidylserines / Q000378:metabolism; D055668:Photochemical Processes; D010778:Photochemotherapy; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D010718:Phosphatidylserines; D011758:Pyrroles; D015363:Quinolones; D004247:DNA